Two overarching themes unite the Portland Alcohol Research Center (PARC) projects and cores. The first is genetic and epigenetic risk factors that contribute to the etiology of alcohol use disorders. The second is the role of genetic and epigenetic factors in the consequences of alcohol use. A major strength is the use of multiple species, which will result in more comprehensive analysis and provide important translational links. A significant focus is on neural mapping via imaging studies in non-human primates and humans, and brain region-specific gene expression studies in mice and macaques. Importantly, we retain our focus on genetic influences on level of chronic alcohol use and neuroadaptation in mice and monkeys, and also introduce a human Project (P001) that will consider genetic family history and brain response to an acute alcohol challenge. We expand our explorations to consideration of the impact of alcohol use on epigenetic marks and consequences for host gene expression. The genetic risk and protective markers, patterns of neural circuitry differences and changes, and epigenetic and gene network information will ultimately help us and others to develop strategies for the prevention and treatment of alcoholism. Our existing genetic and imaging network analyses in mice and/or non-human primates have provided important information about relevant brain regions and pathways, and important gene networks and hubs. This information provides the basis for validation steps to now be undertaken in a new Core (C001) designed for that purpose; C001 will also develop new approaches to study nominated neural mechanisms and pathways as they arise. Four research Projects (P001-P004), two service Cores (C001, C002), and a pilot project Core (C003) address the PARC themes, using mouse models, non-human primates and human subjects. An example of a proposed pilot project is one that will supplement circuit information arising from our expanded focus on imaging in non-human primates and humans, by further developing our ability to perform imaging in mice. An outreach Core (Information Dissemination Core, C004) continues to train pre-doctoral, post-doctoral and medical students in alcohol research, disseminates research findings to the public, and engages in a range of educational activities with elementary to high school students. Our bioinformatics efforts have enabled expansion of a key strength of our group from the analysis of the contributions of individual genes on behavioral functions of the whole organism to include gene network identification; this will continue in Core (C002). In addition, the PARC has an extensive network of collaborations with alcohol researchers at other institutions, including those linked to other Centers and consortia. In summary, the PARC seeks to identify genetic factors and epigenetic changes that place individuals at risk or protect them from alcoholism, and to identify genetic, epigenetic and neural consequences of excessive alcohol use. This knowledge will facilitate intervention and the development of better therapeutics to treat alcohol use disorders.